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US 12,440,576 B2Granted
Antibody drug conjugates comprising sting agonists
AssigneeMersana Therapeutics, Inc.
InventorsJeremy R. Duvall, Keith W. Bentley, Raghida A. Bukhalid, Naniye Cetinbas, Marc I. Damelin, Eugene W. Kelleher, Timothy B. Lowinger, Joshua D. Thomas, Dorin Toader, Ling Xu, Liping Yang
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Abstract
The present disclosure provides scaffolds and antibody-drug conjugates (ADCs) comprising a stimulator of interferon genes (STING). The present disclosure also provides uses of the ADCs in treatment, e.g., treatment of cancer.
Claims20
An antibody-drug conjugate (ADC) being
- or a pharmaceutically acceptable salt or stereoisomer thereof,
- wherein the HER2 antibody comprises a variable heavy chain complementarity determining region 1 (CDRH1) comprising the amino acid sequence FTFSSYSMN (SEQ ID NO:
- 20);
- a variable heavy chain complementarity determining region 2 (CDRH2) comprising the amino acid sequence YISSSSSTIYYADSVKG (SEQ ID NO:
- 21);
- a variable heavy chain complementarity determining region 3 (CDRH3) comprising the amino acid sequence GGHGYFDL (SEQ ID NO:
- 22);
- a variable light chain complementarity determining region 1 (CDRL1) comprising the amino acid sequence RASQSVSSSYLA (SEQ ID NO:
- 27);
- a variable light chain complementarity determining region 2 (CDRL2) comprising the amino acid sequence GASSRAT (SEQ ID NO:
- 28);
- and a variable light chain complementarity determining region 3 (CDRL3) comprising the amino acid sequence QQYHHSPLT (SEQ ID NO:
- 29), and d15 represents an integer ranging from about 1 to about 20.
10 more elements
An antibody-drug conjugate (ADC) being
- or a pharmaceutically acceptable salt or stereoisomer thereof,
- wherein the HER2 antibody comprises a variable heavy chain complementarity determining region 1 (CDRH1) comprising the amino acid sequence FTFSSYSMN (SEQ ID NO:
- 20);
- a variable heavy chain complementarity determining region 2 (CDRH2) comprising the amino acid sequence YISSSSSTIYYADSVKG (SEQ ID NO:
- 21);
- a variable heavy chain complementarity determining region 3 (CDRH3) comprising the amino acid sequence GGHGYFDL (SEQ ID NO:
- 22);
- a variable light chain complementarity determining region 1 (CDRL1) comprising the amino acid sequence RASQSVSSSYLA (SEQ ID NO:
- 27);
- a variable light chain complementarity determining region 2 (CDRL2) comprising the amino acid sequence GASSRAT (SEQ ID NO:
- 28);
- and a variable light chain complementarity determining region 3 (CDRL3) comprising the amino acid sequence QQYHHSPLT (SEQ ID NO:
- 29), and d15 represents an integer ranging from about 1 to about 20.
10 more elements
An antibody-drug conjugate of Formula (I):
- PBRM-[A1-(LC)-D]d15 (I),
- or a pharmaceutically acceptable salt or stereoisomer thereof, wherein:
- A1 is
- wherein * denotes attachment to PBRM and ** denotes attachment to LC;
- LC is
- wherein # denotes attachment to A1 and ## denotes attachment to D;
- MA is
- wherein * denotes attachment to A1, ** denotes attachment to T1, and *** denotes attachment to LD;
- LD is ***—NH—(CH2CH2O)2—(CH2)2—C(O)-(alanine)-****, wherein* denotes attachment to MA and **** denotes attachment to D;
- T1 is
- wherein n4 is 8;
- D is
- wherein R2 is —O—, and
- denotes attachment to LD;
- PBRM is a HER2 antibody comprising a variable heavy chain complementarity determining region 1 (CDRH1) comprising the amino acid sequence FTFSSYSMN (SEQ ID NO:
- 20);
- a variable heavy chain complementarity determining region 2 (CDRH2) comprising the amino acid sequence YISSSSSTIYYADSVKG (SEQ ID NO:
- 21);
- a variable heavy chain complementarity determining region 3 (CDRH3) comprising the amino acid sequence GGHGYFDL (SEQ ID NO:
- 22);
- a variable light chain complementarity determining region 1 (CDRL1) comprising the amino acid sequence RASQSVSSSYLA (SEQ ID NO:
- 27);
- a variable light chain complementarity determining region 2 (CDRL2) comprising the amino acid sequence GASSRAT (SEQ ID NO:
- 28);
- and a variable light chain complementarity determining region 3 (CDRL3) comprising the amino acid sequence QQYHHSPLT (SEQ ID NO:
- 29);
- and
- d15 represents an integer ranging from about 1 to about 20.
25 more elements
Dependencies are inferred from the claim text.